Biological and synthetic materials are used conventionally for generating biomaterials that are employed to grow tissue and for achieving hemostasis. For example, U.S. Pat. No. 5,895,412 to Tucker1 discloses a collagen formulation which, when subject to sufficient elevated temperature, create an effective barrier against blood leaks. U.S. Pat. No. 4,395,396 to Eibl et al. discloses the use of a formulation of blood coagulation factors for hemostasis. Fibrin based materials have also been used as a scaffold for tissue growth (Ye et al, “Fibrin Gel as Three Dimensional Matrix in Cardiovascular Tissue Engineering”, European Journal of Cardio-Thoracic Surgery, vol. 17, pages 87-591 (2000)). 1The entire disclosure of each U.S. patent and other publication cited hereinafter is hereby expressly incorporated hereinto by reference.
In order to grow cells, it has been suggested previously that polymer/salt composites be used to make biocompatible porous polymer membranes, particularly resorbable polymers of poly(L-lactic acid) poly (D,L-lactic acid) and poly(D,L-lactic-co-glycolic acid). (See, Mikos et al. U.S. Pat. No. 5,514,378). Collagen and polyglycolic acid mesh have also been disclosed as a means to construct an artificial esophagus. (See, Miki et al, ASAIO Journal, volume 45, pages 502-508 (1999)).
Surgical adhesive compositions for tissue are also well known as evidenced, for example, by U.S. Pat. No. 5,385,606. In general, such surgical adhesives are achieved by combining a two part system typically comprised of a water soluble proteinaceous material (e.g., albumin, particularly bovine or human serum albumin), and a di- or polyaldehyde (e.g., glutaraldehyde) in appropriate amounts, and allowing the combined mixture to react in situ on the tissue surface or surfaces to be bonded. In this manner, sutureless (or minimally sutured) repairs of tissue wounds, perforations, tears and the like may be achieved.
None of the biomaterials used as cell growth matrices, hemostatic agents or surgical adhesives, however, are expandable in situ by the presence of blowing agents to achieve a foam-like structure. Therefore, it is towards providing such biomaterials and methods that the present invention is directed.
Broadly, the invention disclosed herein is embodied in a liquid, injectable, biomaterial that is transformed in situ to a foam-like, space filling, and adherent hydrogel. More specifically, the present invention is embodied in a two-part liquid system to achieve the in situ formation of a foam-like biomaterial. The liquid system is generally comprised of a protein solution and a cross linker solution which may either be premixed and then applied to a site in need of the biomaterial, or simultaneously mixed and delivered through an in-line mixing/dispensing tip directly to the site.
An expandable foam-like biomaterial is formed in response to the respective liquid components in the two-part liquid system being brought into contact with one another. When the two components are mixed with one another, the resulting biomaterial that is formed in situ adheres to virtually any man-made surface (e.g., surfaces formed of plastic, wood, metal, and chamois materials), as well as to human, plant and animal tissue. The resulting biomaterial exhibits the properties of both a closed-cell-foam and open-cell-foam. In this regard, the presence of closed cells is indicated by the ability of the biomaterial to resiliently recover from deformation to its original shape. The presence of open cells is indicated by its ability to absorb and release liquid (e.g., water, physiological buffers and the like). The foam-like biomaterial is soft to the touch and easily compressible.
These and other aspects and advantages will become more apparent after careful consideration is given to the following detailed description of the preferred exemplary embodiments thereof.